Heritability of Morningness‐Eveningness and Self‐Report Sleep Measures in a Family‐Based Sample of 521 Hutterites

Individual variation in the phase and amplitude of human circadian rhythms is well known, but the impact of heritable factors on such variation is less clear. We estimated the narrow‐sense heritability for selected circadian and sleep timing, quality, and duration measures among related members of the Hutterites, an endogamous, religious community (n=521 participants). “Morningness‐eveningness” (M/E), a stable trait reflecting circadian phase, was evaluated using the Composite Scale (CS). Subjective sleep measures were assessed using the Sleep Timing Questionnaire. Initial analyses reconfirmed the impact of age on M/E. Previously reported correlations between M/E scores and the sleep measures were also noted, demonstrating the construct validity of the questionnaires among the participants. Following corrections for age, gender, and colony of residence, significant narrow‐sense heritability was noted for M/E (23%). The heritability for subjective sleep measures (related to timing, duration, and quality) were statistically significant for all but one variable, and varied between 12.4% and 29.4%. Thus, significant heritable influences on human circadian phase and subjective sleep indices can be detected through family‐based studies. In view of the impact of circadian malfunction on human health, it may be worthwhile to map genetic factors impacting circadian and sleep variation.     

Heritability of morningness-eveningness and self-report sleep measures in a family-based sample of 521 hutterites

Individual variation in the phase and amplitude of human circadian rhythms is well known, but the impact of heritable factors on such variation is less clear. We estimated the narrow-sense heritability for selected circadian and sleep timing, quality, and duration measures among related members of the Hutterites, an endogamous, religious community (n=521 participants). “Morningness-eveningness” (M/E), a stable trait reflecting circadian phase, was evaluated using the Composite Scale (CS). Subjective sleep measures were assessed using the Sleep Timing Questionnaire. Initial analyses reconfirmed the impact of age on M/E. Previously reported correlations between M/E scores and the sleep measures were also noted, demonstrating the construct validity of the questionnaires among the participants. Following corrections for age, gender, and colony of residence, significant narrow-sense heritability was noted for M/E (23%). The heritability for subjective sleep measures (related to timing, duration, and quality) were statistically significant for all but one variable, and varied between 12.4% and 29.4%. Thus, significant heritable influences on human circadian phase and subjective sleep indices can be detected through family-based studies. In view of the impact of circadian malfunction on human health, it may be worthwhile to map genetic factors impacting circadian and sleep variation.     

DIURNAL PREFERENCE AND SLEEP QUALITY: SAME GENES? A STUDY OF YOUNG ADULT TWINS

The aims of this study were to examine the genetic and environmental influences on diurnal preference and sleep quality, the association between these phenotypes, the genetic and environmental influences on this association, and the magnitude of overlap between these influences. Using a twin design, data on diurnal preference (measured by the Morningness-Eveningness Questionnaire) and sleep quality (measured by the Pittsburgh Sleep Quality Index) were collected from 420 monozygotic twins, 773 dizygotic twins, and 329 siblings (mode age?=?20 yrs, range?=?18–27 yrs) from a population-based twin registry across the UK. Univariate analyses indicated that dominance genetic influence accounted for 52% and non-shared environment 48% of variance in diurnal preference. For sleep quality, additive genetic influence explained 43% and non-shared environment 57% of the variance. The bivariate analysis indicated a significant association between greater eveningness preference and poorer sleep quality (r?=?.27). There was substantial overlap in the additive genetic influences on both phenotypes (rA?=?.57), and overlap in the dominance genetic influences common to both phenotypes was almost absolute (rD = .99). Overlap in non-shared environment was much smaller (rE?=?.02). Additive genetic influence accounted for 2% of the association, dominance genetic influence accounted for 94%, and non-shared environmental influences accounted for the remaining 4%. The substantial overlap in genetic influence between these phenotypes indicates that similar genes are important for diurnal preference and sleep quality. Therefore, those genes already known to influence one phenotype may be possible candidates to explore with regards to the other phenotype. (Author correspondence: ps701nh@gold.ac.uk)     

The Effect of Traumatic Brain Injury on the Timing of Sleep

While there have been single case reports of the development of circadian rhythm sleep disorders, most commonly delayed sleep phase syndrome following traumatic brain injury (TBI), to our knowledge there have been no group investigations of changes to sleep timing in this population. The aim of the present study was to investigate sleep timing following TBI using the dim light melatonin onset (DLMO) as a marker of circadian phase and the Morningness‐Eveningness Questionnaire (MEQ) as a measure of sleep‐wake behavior. A sleep‐wake diary was also completed. It was hypothesized that the timing of DLMO would be delayed and that there would be a greater tendency toward eveningness on the MEQ in a post‐acute TBI group (n=10) compared to a gender and age matched control group. Participants were recruited at routine outpatient review appointments (TBI) and from the general population (control) as part of a larger study. They attended the sleep laboratory where questionnaires were completed, some retrospectively, and saliva melatonin samples were collected half‐hourly according to a standard protocol. The results show that the TBI and control groups reported similar habitual sleep times and this was reflected on the MEQ. There was, however, significant variability in the TBI group's change from the pre‐injury to the current MEQ score. The timing of melatonin onset was not different between the groups. While subtle changes (advances or delays) in this small sample may have cancelled each other out, the present study does not provide conclusive objective evidence of shift in circadian timing of sleep following TBI. Furthermore, although participants did report sleep timing changes, it is concluded that the MEQ may not be suitable for use with this cognitively impaired clinical group.     

Effect of circadian rhythm type on serum lipid levels in shift workers: A 5-year cohort study

We investigated how differences in circadian rhythm type affect the health of workers engaged in shift work. Employees, who were newly hired in a steel company between 2007 and 2011, received the Morningness–Eveningness Questionnaire (MEQ) survey. The target participants were 153 male shift workers who were not being treated with any antihyperlipidemic drugs and underwent periodic physical examinations including blood tests at least twice. According to the score of the MEQ at the time of joining the company, we classified the subjects into five types. Longitudinal changes in serum lipid level were estimated among the circadian rhythm types adjusted for age, BMI, and other covariates using a linear mixed model. The regression coefficient of total cholesterol level in the “definitely and moderately morning” group was ?17.83 (95% confidence interval (CI): ?33.42 to ?2.23), and in the “intermediate ‘group’ was ?16.84 [95% CI: ?30.40 to ?3.28], compared to the moderate evening type.” The total cholesterol level was higher in the moderately evening type than in any of the other groups. Between the Morningness–Eveningness (ME) type and Low-density lipoprotein (LDL) cholesterol levels, compared with the “moderately evening type” group, the regression coefficient in the “intermediate type” group was ?16.08 (95% CI: ?28.79 to ?3.37), and in the “definitely and moderately morning type” group was ?17.50 [95% CI: ?32.11 to ?2.88]. The “moderately evening type” group had a higher LDL cholesterol level than any of the other groups. Evening-type circadian rhythm type shift workers are more prone to elevated serum lipid levels.     

Comparison of the Munich Chronotype Questionnaire with the Horne‐Östberg's Morningness‐Eveningness score

We report on results from an Internet survey of sleeping habits in a Dutch population using the Munich Chronotype Questionnaire (MCTQ), supplemented with the Horne‐Östberg Morningness‐Eveningness Questionnaire (MEQ). The MCTQ was completed by 5,055 responders, of which 2,481 also completed the MEQ. MEQ score correlated well with the MCTQ assessment of time of mid‐sleep on free days (MSF; r=? 0.73) and on workdays (MSW; r=? 0.61). MEQ was more strongly correlated with MSF (50% of sleep time) than with sleep onset (0%), rise time (100%), or with any other percentile (10 to 40, 60% to 90%) of sleep on free days. The study shows that chronotype (based on MSF as measured by the MCTQ) strongly correlates with morningness‐eveningness (as measured by the MEQ). However, the MCTQ collects additional detailed information on sleep‐wake behavior under natural conditions.     

松果体昼夜节律生物钟分子机制的研究进展

在各种非哺乳类脊椎动物中 ,松果体起着中枢昼夜节律振荡器的作用。近来 ,在鸟类松果体中相继发现了几种钟基因 ,如Per、Cry、Clock和Bmal等 ,其表达的时间变化规律与哺乳类视交叉上核 (SCN)的非常相似。钟的振荡由其自身调控反馈环路的转录和翻译组成 ,鸟类松果体和哺乳类SCN似乎具有共同的钟振荡基本分子构架 ;若干钟基因产物作为正向或负向调节子影响钟的振荡 ;昼夜性的控时机制同时也需要翻译后事件的参与。这些过程对钟振荡器的稳定性和 /或钟导引的光输入通路有着重要的调控作用     

动物内源褪黑素调控生物节律的研究进展

内源褪黑素对人类和其他哺乳动物的节律行为具有调控功能。生物节律是自然进化赋予生命的基本特征之一,生物体的生命活动受到生物节律的控制与影响。在哺乳动物中,节律调控中心是松果体,其主要功能是合成和分泌褪黑素。褪黑素广泛参与生物体节律行为的调节,本文从褪黑素的产生和作用机制,分别阐述褪黑素对昼夜节律行为和多种年节律行为的调控作用,同时明确褪黑素与生物钟及神经内分泌系统的直接作用和反馈互动的复杂集合,进一步揭示褪黑素调控生物节律的重要作用,以期为褪黑素的基础研究以及未来探究生物体的生物钟内源性发生机制提供参考。     

Exploring the Interdependence of Couples' Rest‐Wake Cycles: An Actigraphic Study

Within western societies, it is commonplace for couples to share a bed. Yet there has been remarkably little research carried out on couples' sleep. This paper draws upon actigraphy, audio diary, and questionnaire data from both partners of 36 heterosexual couples (age 20–59 yrs) and aims to quantify the extent to which it is important to take into account the dyadic nature of sleep‐wake cycles. It achieves this through two interrelated aims: to use hierarchical linear models to measure dyadic interdependence in actigraphically recorded variables, and to investigate how much of this dyadic interdependence truly results from couple dynamics. The variables with the most significant couple interdependency were actual bed time, sleep latency, light/dark ratio, and wake bouts. The paper concludes by suggesting that interdependence may be the defining feature of couples' sleep, and that we need to employ analytic approaches that both acknowledge this and are sensitive to the possibilities that not all aspects of sleep will behave in the same way.     

Sleep biological rhythms in normal infants and those at high risk for SIDS

The focus of this study was on daytime and nighttime sleep and wakefulness during the peak age for Sudden Infant Death Syndrome (SIDS), two to four months, to determine whether there are differences between at-risk for SIDS (R) and control (C) infants. Such differences may provide insight on the frequent occurrence of SIDS in the early morning hours, when most babies are asleep. This is the only study in which R and C infants were continuously monitored for long periods of time (24-48 h) and then followed and recorded at monthly intervals until the age of 4-6 months. Data analyses indicate that ultradian REM/NREM cyclicity becomes stabilized into a regular pattern at three months of age. Infants at this age convert from a polyphasic sleep/wakefulness pattern to a circadian one. Among the changes that occur is a lengthening of short sleep periods that consolidate at night and wake periods that consolidate in the daytime. The most striking effects are related to sleep state and vary according to age and sex. The lengthening of single sleep and wakeful periods is coupled with the maturation of the brain. The development of the central nervous system facilitates the synchronization of sleeping patterns with external light input and social entrainment. One or more biological clocks or oscillators may be responsible for these REM/NREM patterns and circadian cycles. These differences during the early morning hours, when the occurrence of SIDS peaks, may have important implications for understanding the pathophysiological mechanism of SIDS.     

Time-of-Day Mediates the Influences of Extended Wake and Sleep Restriction on Simulated Driving

Although a nonlinear time-of-day and prior wake interaction on performance has been well documented, two recent studies have aimed to incorporate the influences of sleep restriction into this paradigm. Through the use of sleep-restricted forced desynchrony protocols, both studies reported a time-of-day?×?sleep restriction interaction, as well as a time-of-day?×?prior wake?×?sleep dose three-way interaction. The current study aimed to investigate these interactions on simulated driving performance, a more complex task with ecological validity for the problem of fatigued driving. The driving performance of 41 male participants (mean?±?SD: 22.8 ±2.2 yrs) was assessed on a 10-min simulated driving task with the standard deviation of lateral position (SDLAT) measured. Using a between-group design, participants were subjected to either a control condition of 9.33?h of sleep/18.66?h of wake, a moderate sleep-restriction (SR) condition of 7?h of sleep/21?h of wake, or a severe SR condition of 4.66?h of sleep/23.33?h of wake. In each condition, participants were tested at 2.5-h intervals after waking across 7?×?28-h d of forced desynchrony. Driving sessions occurred at nine doses of prior wake, within six divisions of the circadian cycle based on core body temperature (CBT). Mixed-models analyses of variance (ANOVAs) revealed significant main effects of time-of-day, prior wake, sleep debt, and sleep dose on SDLAT. Additionally, significant two-way interactions of time-of-day?×?prior wake and time-of-day?×?sleep debt, as well as significant three-way interactions of time-of-day?×?prior wake?×?sleep debt and time-of-day?×?sleep debt?×?sleep dose were observed. Although limitations such as the presence of practice effects and large standard errors are noted, the study concludes with three findings. The main effects demonstrate that extending wake, reducing sleep, and driving at poor times of day all significantly impair driving performance at an individual level. In addition to this, combining either extended wake or a sleep debt with the early morning hours greatly decreases driving performance. Finally, operating under the influence of a reduced sleep dose can greatly decrease performance at all times of the day. (Author correspondence: raymond.matthews@unisa.edu.au)     

Twelve-Hour Night Shifts of Healthcare Workers: A Risk to the Patients?

We assessed the impact of 12h fixed night shift (19:00–07:00h) work, followed by 36h of off-time, on the sleep–wake cycle, sleep duration, self-perceived sleep quality, and work-time alertness on a group composed of 5 registered and 15 practical nurses. Wrist actigraphy (Ambulatory Monitoring, Inc.), with data analysis by the Cole-Kripke algorithm, was applied to determine sleep/wake episodes and their duration. The sleep episodes were divided into six categories: sleep during the night shift (x¯=208.6; SD±90.6mins), sleep after the night shift (x¯=138.7; SD±79.6min), sleep during the first night after the night work (x¯=318.5; SD±134.6min), sleep before the night work (x¯=104.3; SD±44.1min), diurnal sleep during the rest day (x¯=70.5; SD±43.0min), and nocturnal sleep during the rest day (x¯=310.4; SD±188.9mins). A significant difference (p<.0001; T-test for dependent samples) was detected between the perceived quality of sleep of the three diurnal sleep categories compared to the three nocturnal sleep categories. Even thought the nurses slept (napped) during the night shift, their self-perceived alertness systematically decreased during it. Statistically significant differences were documented by one-way ANOVA (F=40.534 p<.0001) among the alertness measurements done during the night shift. In particular, there was significant difference in the level of perceived alertness (p<.0001) between the 7^th and 10^thh of the 12h night shift. These findings of decreased alertness during the terminal hours of the night shift are of concern, since they suggest risk of comprised patient care.     

The influence of the sleep-wake cycle on primary monosymptomatic nocturnal enuresis: a non-randomized comparative study

Backround: Enuresis implies severe stress in affected children, and impairs quality of life and sleep. Children with enuresis experience difficulties in their arousal from sleep, possibly associated with disturbances of the circadian rhythm. In this study, we aimed to evaluate the sleep–wake cycle and sleep disturbances in children with monosymptomatic enuresis nocturna (MEN). Method: The study comprised 70 children with MEN who were admitted to the pediatrics and urology outpatients department and 94 age-matched healthy controls. Parents completed “Strengths and Difficulties Questionnaire,” Children’s Sleep Habits Questionnaire (CSHQ), Children’s Chronotype Questionnaire scale. Results: Children with enuresis had significantly more sleep and psychological problem. Enuresis group reported higher bedtime resistance, parasomnias, breathing-related problems, and daytime sleepiness in CHSQ (p < 0.05). Although circadian preference did not differ statistically between the groups (p > 0.05), sleep duration on school days and awakening and mid-sleep points, both on scheduled and free days, were found to be significantly different in the enuretic group (p < 0.05). In logistic regression analysis, age, sleep period on scheduled days, sleep inertia on scheduled and free days were significant predictor for enuresis. Discussion: Children with enuresis were more likely to experience problematic sleep. This may reflect that enuretic children have impaired sleep–wake cycles, leading to dysregulation of daily functional changes of bladder capacity and related hormones such as ADH. These findings might imply a sleep–wake disturbance in enuresis.     

Hypocretins: The Timing of Sleep and Waking

The appropriate time and place for sleep and waking are important factors for survival. Sleep and waking, rest and activity, flight and fight, feeding, and reproduction are all organized in relation to the day and night. A biological clock, the suprachiasmatic nucleus (SCN), synchronized by photic influences and other environmental cues, provides an endogenous timing signal that entrains circadian body rhythms and is complemented by a homeostatic sleep pressure factor. Cholinergic, catecholaminergic, serotonergic, and histaminergic nuclei control wakefulness and mutually interact with the SCN as well as sleep‐ and wake‐promoting neurons in the hypothalamus to form a bistable switch that controlls the timing of behavioral state transitions. Hypocretin neurons integrate circadian‐photic and nutritional‐metabolic influences and act as a conductor in the aminergic orchestra. Their loss causes narcolepsy, a disease conferring the inability to separate sleep and waking. Their role in appetitive behavior, stress, and memory functions is important to our understanding of addiction and compulsion.     

The Function of Circadian RNA‐Binding Proteins and Their cis‐Acting Elements in Microalgae

An endogenous clock regulates the temporal expression of genes/mRNAs that are involved in the circadian output pathway. In the bioluminescent dinoflagellate Gonyaulax polyedra circadian expression of the luciferin‐binding protein (LBP) is controlled at the translational level. Thereby, a clock‐controlled RNA‐binding protein, called circadian controlled translational regulator (CCTR), interacts specifically with an UG‐repeat, which is situated in the lbp 3^′ UTR. Its binding activity correlates negatively with the amount of LBP during a circadian cycle. In the green alga Chlamydomonas reinhardtii, a clock‐controlled RNA‐binding protein (CHLAMY 1) was identified, which represents an analog of the CCTR from the phylogenetically diverse alga G. polyedra. CHLAMY 1 binds specifically to the 3^′ UTRs of several mRNAs and recognizes them all via a common cis‐acting element, composed of at least seven UG‐repeats. The binding strength of CHLAMY 1 is strongest to mRNAs, whose products are key components of nitrogen metabolism resulting in arginine biosynthesis as well as of CO₂ metabolism. Since temporal activities of processes involved in nitrogen metabolism have an opposite phase than CHLAMY 1 binding activity, the protein might repress the translation of the cognate mRNAs.